Sialiuria (Sialuria) - Gen GNE.  

The sialuria is a rare disorder that has variable effects on development. Affected children are often born with neonatal jaundice, hepatosplenomegaly and microcytic anemia. Affected individuals may have a somewhat flat face and distinctive facial features. Some individuals have developmental delay and hypotonia.

Sialuria young children tend to have frequent respiratory infections and episodes of dehydration and gastroenteritis. Older children may have seizures and learning difficulties. In some affected children, intellectual development is almost normal. The characteristics of the sialuria vary among affected people. Many of the problems associated with this disorder seem to improve with age, but little about the long - term effects of the disease is known.

This process is due to mutations in the GNE gene, located on the short arm of chromosome 9 (9p13.3). This gene encodes an enzyme found in cells and tissues, which is involved in a chemical pathway that produces sialic acid, a carbohydrate that binds to the ends of more complex molecules located on the surface of cells. By modifying these molecules, sialic acid affects a wide variety of cellular functions including migration, adhesion and cell signaling and inflammation.

Several mutations have been identified in the GNE gene causing sialuria. Each of these mutations change a single amino acid in the region allosteric enzyme. This region is critical for normal regulation of the enzyme. The enzyme produced from the GNE gene controls which cells produce an appropriate amount of sialic acid. When more sialic acid is not required, a feedback system decreases the activity of the enzyme. Mutations responsible sialuria interrupt this feedback mechanism, resulting in an overproduction of sialic acid. This carbohydrate accumulates within cells and is excreted in the urine. Work is being done to determine how an accumulation of sialic acid in the body interferes with normal development in people with sialuria.

This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the alteration. Most reported cases have occurred in people with no known history of the disease in their family and may be the result of new mutations in the gene.

Tests in IVAMI: in IVAMI perform detection of mutations associated with sialuria, by complete PCR amplification of exons GNE gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).